摘要
表观遗传学定义为体细胞可遗传的变化，不伴随DNA序列的改变。表观遗传学包括DNA甲基化，共价组蛋白修饰，非编码RNA以及核小体重塑。值得注意的是，异常的表观遗传变化在癌症发展中起着关键作用，包括恶性转化，转移，预后，耐药性和肿瘤复发，这些都可以为癌症的预后，诊断和治疗提供有效的靶点。了解这些变化为癌症诊断提供了有效手段，并为更好的临床应用提供了药物治疗目标。近年来，已发现组蛋白修饰和相关酶与癌症发病率和预后良好相关。组蛋白修饰酶的失调表达或突变以及组蛋白修饰状态异常被认为在肿瘤发生和癌症治疗的临床结果中起重要作用。一些组蛋白修饰抑制剂已广泛用于临床实践中，并且许多其他抑制剂仍在实验室研究或临床前评估中。在这里，我们总结了表观遗传学的重要作用，特别是组蛋白修饰在癌症诊断和治疗方面的作用，并讨论了可激活的表观遗传靶标在癌症治疗学中的发展意义。
关键词: 癌症治疗学，表观遗传学，表观遗传调节剂，组蛋白修饰，组蛋白修饰，癌症治疗。
[1]
Feinberg, A.P.; Koldobskiy, M.A.; Göndör, A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat. Rev. Genet., 2016, 17(5), 284-299.
[2]
Ordovás, J.M.; Smith, C.E. Epigenetics and cardiovascular disease. Nat. Rev. Cardiol., 2010, 7(9), 510-519.
[3]
Broen, J.C.; Radstake, T.R.; Rossato, M. The role of genetics and epigenetics in the pathogenesis of systemic sclerosis. Nat. Rev. Rheumatol., 2014, 10(11), 671-681.
[4]
Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21(3), 381-395.
[5]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[6]
Dawson, M.A.; Kouzarides, T. Cancer epigenetics: from mechanism to therapy. Cell, 2012, 150(1), 12-27.
[7]
Rodríguez-Paredes, M.; Esteller, M. Cancer epigenetics reaches mainstream oncology. Nat. Med., 2011, 17(3), 330-339.
[8]
Gaudet, F.; Hodgson, J.G.; Eden, A.; Jackson-Grusby, L.; Dausman, J.; Gray, J.W.; Leonhardt, H.; Jaenisch, R. Induction of tumors in mice by genomic hypomethylation. Science, 2003, 300(5618), 489-492.
[9]
Eden, A.; Gaudet, F.; Waghmare, A.; Jaenisch, R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science, 2003, 300(5618), 455.
[10]
Esteller, M.; Corn, P.G.; Baylin, S.B.; Herman, J.G. A gene hypermethylation profile of human cancer. Cancer Res., 2001, 61(8), 3225-3229.
[11]
Fandy, T.E. Development of DNA methyltransferase inhibitors for the treatment of neoplastic diseases. Curr. Med. Chem., 2009, 16(17), 2075-2085.
[12]
Fraga, M.F.; Ballestar, E.; Villar-Garea, A.; Boix-Chornet, M.; Espada, J.; Schotta, G.; Bonaldi, T.; Haydon, C.; Ropero, S.; Petrie, K.; Iyer, N.G.; Pérez-Rosado, A.; Calvo, E.; Lopez, J.A.; Cano, A.; Calasanz, M.J.; Colomer, D.; Piris, M.A.; Ahn, N.; Imhof, A.; Caldas, C.; Jenuwein, T.; Esteller, M. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet., 2005, 37(4), 391-400.
[13]
Seligson, D.B.; Horvath, S.; McBrian, M.A.; Mah, V.; Yu, H.; Tze, S.; Wang, Q.; Chia, D.; Goodglick, L.; Kurdistani, S.K. Global levels of histone modifications predict prognosis in different cancers. Am. J. Pathol., 2009, 174(5), 1619-1628.
[14]
Huang, Y.; Rao, A. Connections between TET proteins and aberrant DNA modification in cancer. Trends Genet., 2014, 30(10), 464-474.
[15]
Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat. Rev. Genet., 2007, 8(4), 286-298.
[16]
Marks, P.; Rifkind, R.A.; Richon, V.M.; Breslow, R.; Miller, T.; Kelly, W.K. Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer, 2001, 1(3), 194-202.
[17]
Minucci, S.; Pelicci, P.G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer, 2006, 6(1), 38-51.
[18]
Falkenberg, K.J.; Johnstone, R.W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov., 2014, 13(9), 673-691.
[19]
Jones, P.A.; Issa, J-P.J.; Baylin, S. Targeting the cancer epigenome for therapy. Nat. Rev. Genet., 2016, 17(10), 630-641.
[20]
Plass, C.; Pfister, S.M.; Lindroth, A.M.; Bogatyrova, O.; Claus, R.; Lichter, P. Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat. Rev. Genet., 2013, 14(11), 765-780.
[21]
Varambally, S.; Dhanasekaran, S.M.; Zhou, M.; Barrette, T.R.; Kumar-Sinha, C.; Sanda, M.G.; Ghosh, D.; Pienta, K.J.; Sewalt, R.G.; Otte, A.P.; Rubin, M.A.; Chinnaiyan, A.M. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature, 2002, 419(6907), 624-629.
[22]
Chase, A.; Cross, N.C. Aberrations of EZH2 in cancer. Clin. Cancer Res., 2011, 17(9), 2613-2618.
[24]
Elsheikh, S.E.; Green, A.R.; Rakha, E.A.; Powe, D.G.; Ahmed, R.A.; Collins, H.M.; Soria, D.; Garibaldi, J.M.; Paish, C.E.; Ammar, A.A.; Grainge, M.J.; Ball, G.R.; Abdelghany, M.K.; Martinez-Pomares, L.; Heery, D.M.; Ellis, I.O. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res., 2009, 69(9), 3802-3809.
[25]
Van Den Broeck, A.; Brambilla, E.; Moro-Sibilot, D.; Lantuejoul, S.; Brambilla, C.; Eymin, B.; Khochbin, S.; Gazzeri, S. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin. Cancer Res., 2008, 14(22), 7237-7245.
[26]
Manuyakorn, A.; Paulus, R.; Farrell, J.; Dawson, N.A.; Tze, S.; Cheung-Lau, G.; Hines, O.J.; Reber, H.; Seligson, D.B.; Horvath, S.; Kurdistani, S.K.; Guha, C.; Dawson, D.W. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J. Clin. Oncol., 2010, 28(8), 1358-1365.
[27]
Farria, A.; Li, W.; Dent, S.Y. KATs in cancer: functions and therapies. Oncogene, 2015, 34(38), 4901-4913.
[28]
Fei, H.J.; Zu, L.D.; Wu, J.; Jiang, X.S.; Wang, J.L.; Chin, Y.E.; Fu, G.H. PCAF acts as a gastric cancer suppressor through a novel PCAF-p16-CDK4 axis. Am. J. Cancer Res., 2016, 6(12), 2772-2786.
[29]
Wan, J.; Xu, W.; Zhan, J.; Ma, J.; Li, X.; Xie, Y.; Wang, J.; Zhu, W.G.; Luo, J.; Zhang, H. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6. Nucleic Acids Res., 2016, 44(22), 10662-10675.
[30]
Malatesta, M.; Steinhauer, C.; Mohammad, F.; Pandey, D.P.; Squatrito, M.; Helin, K. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation. Cancer Res., 2013, 73(20), 6323-6333.
[31]
Cheng, G.; Liu, F.; Asai, T.; Lai, F.; Man, N.; Xu, H.; Chen, S.; Greenblatt, S.; Hamard, P.J.; Ando, K.; Chen, X.; Wang, L.; Martinez, C.; Tadi, M.; Wang, L.; Xu, M.; Yang, F.C.; Shiekhattar, R.; Nimer, S.D. Loss of p300 accelerates MDS-associated leukemogenesis. Leukemia, 2017, 31(6), 1382-1390.
[32]
Gayther, S.A.; Batley, S.J.; Linger, L.; Bannister, A.; Thorpe, K.; Chin, S-F.; Daigo, Y.; Russell, P.; Wilson, A.; Sowter, H.M.; Delhanty, J.D.; Ponder, B.A.; Kouzarides, T.; Caldas, C. Mutations truncating the EP300 acetylase in human cancers. Nat. Genet., 2000, 24(3), 300-303.
[33]
Pattabiraman, D.R.; McGirr, C.; Shakhbazov, K.; Barbier, V.; Krishnan, K.; Mukhopadhyay, P.; Hawthorne, P.; Trezise, A.; Ding, J.; Grimmond, S.M.; Papathanasiou, P.; Alexander, W.S.; Perkins, A.C.; Levesque, J.P.; Winkler, I.G.; Gonda, T.J. Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes. Blood, 2014, 123(17), 2682-2690.
[34]
Yang, H.; Pinello, C.E.; Luo, J.; Li, D.; Wang, Y.; Zhao, L.Y.; Jahn, S.C.; Saldanha, S.A.; Chase, P.; Planck, J.; Geary, K.R.; Ma, H.; Law, B.K.; Roush, W.R.; Hodder, P.; Liao, D. Small-molecule inhibitors of acetyltransferase p300 identified by high-throughput screening are potent anticancer agents. Mol. Cancer Ther., 2013, 12(5), 610-620.
[35]
Yang, X.J.; Seto, E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene, 2007, 26(37), 5310-5318.
[36]
Lau, O.D.; Kundu, T.K.; Soccio, R.E.; Ait-Si-Ali, S.; Khalil, E.M.; Vassilev, A.; Wolffe, A.P.; Nakatani, Y.; Roeder, R.G.; Cole, P.A. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol. Cell, 2000, 5(3), 589-595.
[37]
Marcu, M.G.; Jung, Y.J.; Lee, S.; Chung, E.J.; Lee, M.J.; Trepel, J.; Neckers, L. Curcumin is an inhibitor of p300 histone acetyltransferase. Med. Chem., 2006, 2(2), 169-174.
[38]
Balasubramanyam, K.; Altaf, M.; Varier, R.A.; Swaminathan, V.; Ravindran, A.; Sadhale, P.P.; Kundu, T.K. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J. Biol. Chem., 2004, 279(32), 33716-33726.
[39]
Sun, Y.; Jiang, X.; Chen, S.; Price, B.D. Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett., 2006, 580(18), 4353-4356.
[40]
Li, Z.; Zhu, W-G. Targeting histone deacetylases for cancer therapy: from molecular mechanisms to clinical implications. Int. J. Biol. Sci., 2014, 10(7), 757-770.
[41]
Guha, M. HDAC inhibitors still need a home run, despite recent approval. Nat. Rev. Drug Discov., 2015, 14(4), 225-226.
[42]
Göttlicher, M.; Minucci, S.; Zhu, P.; Krämer, O.H.; Schimpf, A.; Giavara, S.; Sleeman, J.P.; Lo Coco, F.; Nervi, C.; Pelicci, P.G.; Heinzel, T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J., 2001, 20(24), 6969-6978.
[43]
Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, E.M.; Ferrara, F.; Bresciani, F.; Weisz, A.; de Lera, A.R.; Gronemeyer, H.; Altucci, L. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat. Med., 2005, 11(1), 77-84.
[44]
Lee, J.H.; Choy, M.L.; Ngo, L.; Foster, S.S.; Marks, P.A. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc. Natl. Acad. Sci. USA, 2010, 107(33), 14639-14644.
[45]
Namdar, M.; Perez, G.; Ngo, L.; Marks, P.A. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc. Natl. Acad. Sci. USA, 2010, 107(46), 20003-20008.
[46]
Pathania, R.; Kolhe, R.B.; Ramachandran, S.; Mariappan, G.; Thakur, P.; Prasad, P.D.; Ganapathy, V.; Thangaraju, M. Combination of DNMT and HDAC inhibitors reprogram cancer stem cell signaling to overcome drug resistance. Cancer Res., 2016, 76(11), 3224-3235.
[47]
Zhu, W.G.; Lakshmanan, R.R.; Beal, M.D.; Otterson, G.A. DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res., 2001, 61(4), 1327-1333.
[48]
Zhu, W-G.; Otterson, G.A. The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells. Curr. Med. Chem. Anticancer Agents, 2003, 3(3), 187-199.
[49]
Zhao, Y.; Lu, S.; Wu, L.; Chai, G.; Wang, H.; Chen, Y.; Sun, J.; Yu, Y.; Zhou, W.; Zheng, Q.; Wu, M.; Otterson, G.A.; Zhu, W.G. Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1). Mol. Cell. Biol., 2006, 26(7), 2782-2790.
[50]
Wu, L.P.; Wang, X.; Li, L.; Zhao, Y.; Lu, S.; Yu, Y.; Zhou, W.; Liu, X.; Yang, J.; Zheng, Z.; Zhang, H.; Feng, J.; Yang, Y.; Wang, H.; Zhu, W.G. Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter. Mol. Cell. Biol., 2008, 28(10), 3219-3235.
[51]
Yang, Y.; Zhao, Y.; Liao, W.; Yang, J.; Wu, L.; Zheng, Z.; Yu, Y.; Zhou, W.; Li, L.; Feng, J.; Wang, H.; Zhu, W.G. Acetylation of FoxO1 activates Bim expression to induce apoptosis in response to histone deacetylase inhibitor depsipeptide treatment. Neoplasia, 2009, 11(4), 313-324.
[52]
Wang, H.; Zhou, W.; Zheng, Z.; Zhang, P.; Tu, B.; He, Q.; Zhu, W-G. The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage. DNA Repair (Amst.), 2012, 11(2), 146-156.
[53]
Yao, Y.; Yang, Y.; Zhu, W-G. Sirtuins: nodes connecting aging, metabolism and tumorigenesis. Curr. Pharm. Des., 2014, 20(11), 1614-1624.
[54]
Liu, X.; Wang, D.; Zhao, Y.; Tu, B.; Zheng, Z.; Wang, L.; Wang, H.; Gu, W.; Roeder, R.G.; Zhu, W-G. Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1). Proc. Natl. Acad. Sci. USA, 2011, 108(5), 1925-1930.
[55]
Zhao, Y.; Yang, J.; Liao, W.; Liu, X.; Zhang, H.; Wang, S.; Wang, D.; Feng, J.; Yu, L.; Zhu, W-G. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat. Cell Biol., 2010, 12(7), 665-675.
[56]
Zhang, P.; Tu, B.; Wang, H.; Cao, Z.; Tang, M.; Zhang, C.; Gu, B.; Li, Z.; Wang, L.; Yang, Y.; Zhao, Y.; Wang, H.; Luo, J.; Deng, C.X.; Gao, B.; Roeder, R.G.; Zhu, W.G. Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion. Proc. Natl. Acad. Sci. USA, 2014, 111(29), 10684-10689.
[57]
Tang, M.; Lu, X.; Zhang, C.; Du, C.; Cao, L.; Hou, T.; Li, Z.; Tu, B.; Cao, Z.; Li, Y.; Chen, Y.; Jiang, L.; Wang, H.; Wang, L.; Liu, B.; Xu, X.; Luo, J.; Wang, J.; Gu, J.; Wang, H.; Zhu, W.G. Downregulation of SIRT7 by 5-fluorouracil induces radiosensitivity in human colorectal cancer. Theranostics, 2017, 7(5), 1346-1359.
[58]
Chen, Y.; Zhu, W.G. Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage. Acta Biochim. Biophys. Sin. (Shanghai), 2016, 48(7), 603-616.
[59]
Kouzarides, T. Histone methylation in transcriptional control. Curr. Opin. Genet. Dev., 2002, 12(2), 198-209.
[60]
Martin, C.; Zhang, Y. The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol., 2005, 6(11), 838-849.
[61]
Greer, E.L.; Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat. Rev. Genet., 2012, 13(5), 343-357.
[62]
Ellinger, J.; Kahl, P.; von der Gathen, J.; Rogenhofer, S.; Heukamp, L.C.; Gütgemann, I.; Walter, B.; Hofstädter, F.; Büttner, R.; Müller, S.C.; Bastian, P.J.; von Ruecker, A. Global levels of histone modifications predict prostate cancer recurrence. Prostate, 2010, 70(1), 61-69.
[63]
Cejas, P.; Cavazza, A.; Yandava, C.; Moreno, V.; Horst, D.; Moreno-Rubio, J.; Burgos, E.; Mendiola, M.; Taing, L.; Goel, A.; Feliu, J.; Shivdasani, R.A. Transcriptional regulator CNOT3 defines an aggressive colorectal cancer subtype. Cancer Res., 2016, 77(3), 766-779.
[64]
Krivtsov, A.V.; Armstrong, S.A. MLL translocations, histone modifications and leukaemia stem-cell development. Nat. Rev. Cancer, 2007, 7(11), 823-833.
[65]
Rao, R.C.; Dou, Y. Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat. Rev. Cancer, 2015, 15(6), 334-346.
[66]
Andersson, A.K.; Ma, J.; Wang, J.; Chen, X.; Gedman, A.L.; Dang, J.; Nakitandwe, J.; Holmfeldt, L.; Parker, M.; Easton, J.; Huether, R.; Kriwacki, R.; Rusch, M.; Wu, G.; Li, Y.; Mulder, H.; Raimondi, S.; Pounds, S.; Kang, G.; Shi, L.; Becksfort, J.; Gupta, P.; Payne-Turner, D.; Vadodaria, B.; Boggs, K.; Yergeau, D.; Manne, J.; Song, G.; Edmonson, M.; Nagahawatte, P.; Wei, L.; Cheng, C.; Pei, D.; Sutton, R.; Venn, N.C.; Chetcuti, A.; Rush, A.; Catchpoole, D.; Heldrup, J.; Fioretos, T.; Lu, C.; Ding, L.; Pui, C.H.; Shurtleff, S.; Mullighan, C.G.; Mardis, E.R.; Wilson, R.K.; Gruber, T.A.; Zhang, J.; Downing, J.R. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat. Genet., 2015, 47(4), 330-337.
[67]
Meyer, C.; Hofmann, J.; Burmeister, T.; Gröger, D.; Park, T.S.; Emerenciano, M.; Pombo de Oliveira, M.; Renneville, A.; Villarese, P.; Macintyre, E.; Cavé, H.; Clappier, E.; Mass-Malo, K.; Zuna, J.; Trka, J.; De Braekeleer, E.; De Braekeleer, M.; Oh, S.H.; Tsaur, G.; Fechina, L.; van der Velden, V.H.; van Dongen, J.J.; Delabesse, E.; Binato, R.; Silva, M.L.; Kustanovich, A.; Aleinikova, O.; Harris, M.H.; Lund-Aho, T.; Juvonen, V.; Heidenreich, O.; Vormoor, J.; Choi, W.W.; Jarosova, M.; Kolenova, A.; Bueno, C.; Menendez, P.; Wehner, S.; Eckert, C.; Talmant, P.; Tondeur, S.; Lippert, E.; Launay, E.; Henry, C.; Ballerini, P.; Lapillone, H.; Callanan, M.B.; Cayuela, J.M.; Herbaux, C.; Cazzaniga, G.; Kakadiya, P.M.; Bohlander, S.; Ahlmann, M.; Choi, J.R.; Gameiro, P.; Lee, D.S.; Krauter, J.; Cornillet-Lefebvre, P.; Te Kronnie, G.; Schäfer, B.W.; Kubetzko, S.; Alonso, C.N.; zur Stadt, U.; Sutton, R.; Venn, N.C.; Izraeli, S.; Trakhtenbrot, L.; Madsen, H.O.; Archer, P.; Hancock, J.; Cerveira, N.; Teixeira, M.R.; Lo Nigro, L.; Möricke, A.; Stanulla, M.; Schrappe, M.; Sedék, L.; Szczepański, T.; Zwaan, C.M.; Coenen, E.A.; van den Heuvel-Eibrink, M.M.; Strehl, S.; Dworzak, M.; Panzer-Grümayer, R.; Dingermann, T.; Klingebiel, T.; Marschalek, R. The MLL recombinome of acute leukemias in 2013. Leukemia, 2013, 27(11), 2165-2176.
[68]
Morin, R.D.; Mendez-Lago, M.; Mungall, A.J.; Goya, R.; Mungall, K.L.; Corbett, R.D.; Johnson, N.A.; Severson, T.M.; Chiu, R.; Field, M.; Jackman, S.; Krzywinski, M.; Scott, D.W.; Trinh, D.L.; Tamura-Wells, J.; Li, S.; Firme, M.R.; Rogic, S.; Griffith, M.; Chan, S.; Yakovenko, O.; Meyer, I.M.; Zhao, E.Y.; Smailus, D.; Moksa, M.; Chittaranjan, S.; Rimsza, L.; Brooks-Wilson, A.; Spinelli, J.J.; Ben-Neriah, S.; Meissner, B.; Woolcock, B.; Boyle, M.; McDonald, H.; Tam, A.; Zhao, Y.; Delaney, A.; Zeng, T.; Tse, K.; Butterfield, Y.; Birol, I.; Holt, R.; Schein, J.; Horsman, D.E.; Moore, R.; Jones, S.J.; Connors, J.M.; Hirst, M.; Gascoyne, R.D.; Marra, M.A. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature, 2011, 476(7360), 298-303.
[69]
Hamamoto, R.; Furukawa, Y.; Morita, M.; Iimura, Y.; Silva, F.P.; Li, M.; Yagyu, R.; Nakamura, Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol., 2004, 6(8), 731-740.
[70]
Hamamoto, R.; Silva, F.P.; Tsuge, M.; Nishidate, T.; Katagiri, T.; Nakamura, Y.; Furukawa, Y. Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci., 2006, 97(2), 113-118.
[71]
Silva, F.P.; Hamamoto, R.; Kunizaki, M.; Tsuge, M.; Nakamura, Y.; Furukawa, Y. Enhanced methyltransferase activity of SMYD3 by the cleavage of its N-terminal region in human cancer cells. Oncogene, 2008, 27(19), 2686-2692.
[72]
Kurash, J.K.; Lei, H.; Shen, Q.; Marston, W.L.; Granda, B.W.; Fan, H.; Wall, D.; Li, E.; Gaudet, F. Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo. Mol. Cell, 2008, 29(3), 392-400.
[73]
Wang, D.; Zhou, J.; Liu, X.; Lu, D.; Shen, C.; Du, Y.; Wei, F.Z.; Song, B.; Lu, X.; Yu, Y.; Wang, L.; Zhao, Y.; Wang, H.; Yang, Y.; Akiyama, Y.; Zhang, H.; Zhu, W.G. Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability. Proc. Natl. Acad. Sci. USA, 2013, 110(14), 5516-5521.
[74]
Shen, C.; Wang, D.; Liu, X.; Gu, B.; Du, Y.; Wei, F.Z.; Cao, L.L.; Song, B.; Lu, X.; Yang, Q.; Zhu, Q.; Hou, T.; Li, M.; Wang, L.; Wang, H.; Zhao, Y.; Yang, Y.; Zhu, W.G. SET7/9 regulates cancer cell proliferation by influencing β-catenin stability. FASEB J., 2015, 29(10), 4313-4323.
[75]
van Zutven, L.J.; Önen, E.; Velthuizen, S.C.; van Drunen, E.; von Bergh, A.R.; van den Heuvel-Eibrink, M.M.; Veronese, A.; Mecucci, C.; Negrini, M.; de Greef, G.E.; Beverloo, H.B. Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. Genes Chromosomes Cancer, 2006, 45(5), 437-446.
[76]
Xiang, Y.; Zhu, Z.; Han, G.; Ye, X.; Xu, B.; Peng, Z.; Ma, Y.; Yu, Y.; Lin, H.; Chen, A.P.; Chen, C.D. JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proc. Natl. Acad. Sci. USA, 2007, 104(49), 19226-19231.
[77]
Yamamoto, S.; Wu, Z.; Russnes, H.G.; Takagi, S.; Peluffo, G.; Vaske, C.; Zhao, X.; Moen Vollan, H.K.; Maruyama, R.; Ekram, M.B.; Sun, H.; Kim, J.H.; Carver, K.; Zucca, M.; Feng, J.; Almendro, V.; Bessarabova, M.; Rueda, O.M.; Nikolsky, Y.; Caldas, C.; Liu, X.S.; Polyak, K. JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell, 2014, 25(6), 762-777.
[78]
Yamane, K.; Tateishi, K.; Klose, R.J.; Fang, J.; Fabrizio, L.A.; Erdjument-Bromage, H.; Taylor-Papadimitriou, J.; Tempst, P.; Zhang, Y. PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol. Cell, 2007, 25(6), 801-812.
[79]
Dalgliesh, G.L.; Furge, K.; Greenman, C.; Chen, L.; Bignell, G.; Butler, A.; Davies, H.; Edkins, S.; Hardy, C.; Latimer, C.; Teague, J.; Andrews, J.; Barthorpe, S.; Beare, D.; Buck, G.; Campbell, P.J.; Forbes, S.; Jia, M.; Jones, D.; Knott, H.; Kok, C.Y.; Lau, K.W.; Leroy, C.; Lin, M.L.; McBride, D.J.; Maddison, M.; Maguire, S.; McLay, K.; Menzies, A.; Mironenko, T.; Mulderrig, L.; Mudie, L.; O’Meara, S.; Pleasance, E.; Rajasingham, A.; Shepherd, R.; Smith, R.; Stebbings, L.; Stephens, P.; Tang, G.; Tarpey, P.S.; Turrell, K.; Dykema, K.J.; Khoo, S.K.; Petillo, D.; Wondergem, B.; Anema, J.; Kahnoski, R.J.; Teh, B.T.; Stratton, M.R.; Futreal, P.A. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature, 2010, 463(7279), 360-363.
[80]
Li, N.; Dhar, S.S.; Chen, T.Y.; Kan, P.Y.; Wei, Y.; Kim, J.H.; Chan, C.H.; Lin, H.K.; Hung, M.C.; Lee, M.G. JARID1D Is a suppressor and prognostic marker of prostate cancer invasion and metastasis. Cancer Res., 2016, 76(4), 831-843.
[81]
Vinogradova, M.; Gehling, V.S.; Gustafson, A.; Arora, S.; Tindell, C.A.; Wilson, C.; Williamson, K.E.; Guler, G.D.; Gangurde, P.; Manieri, W.; Busby, J.; Flynn, E.M.; Lan, F.; Kim, H.J.; Odate, S.; Cochran, A.G.; Liu, Y.; Wongchenko, M.; Yang, Y.; Cheung, T.K.; Maile, T.M.; Lau, T.; Costa, M.; Hegde, G.V.; Jackson, E.; Pitti, R.; Arnott, D.; Bailey, C.; Bellon, S.; Cummings, R.T.; Albrecht, B.K.; Harmange, J.C.; Kiefer, J.R.; Trojer, P.; Classon, M. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat. Chem. Biol., 2016, 12(7), 531-538.
[82]
Metzger, E.; Wissmann, M.; Yin, N.; Müller, J.M.; Schneider, R.; Peters, A.H.; Günther, T.; Buettner, R.; Schüle, R. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature, 2005, 437(7057), 436-439.
[83]
Hayami, S.; Kelly, J.D.; Cho, H.S.; Yoshimatsu, M.; Unoki, M.; Tsunoda, T.; Field, H.I.; Neal, D.E.; Yamaue, H.; Ponder, B.A.; Nakamura, Y.; Hamamoto, R. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int. J. Cancer, 2011, 128(3), 574-586.
[84]
Harris, W.J.; Huang, X.; Lynch, J.T.; Spencer, G.J.; Hitchin, J.R.; Li, Y.; Ciceri, F.; Blaser, J.G.; Greystoke, B.F.; Jordan, A.M.; Miller, C.J.; Ogilvie, D.J.; Somervaille, T.C. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell, 2012, 21(4), 473-487.
[85]
Schenk, T.; Chen, W.C.; Göllner, S.; Howell, L.; Jin, L.; Hebestreit, K.; Klein, H-U.; Popescu, A.C.; Burnett, A.; Mills, K.; Casero, R.A., Jr; Marton, L.; Woster, P.; Minden, M.D.; Dugas, M.; Wang, J.C.; Dick, J.E.; Müller-Tidow, C.; Petrie, K.; Zelent, A. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat. Med., 2012, 18(4), 605-611.
[86]
Wang, J.; Lu, F.; Ren, Q.; Sun, H.; Xu, Z.; Lan, R.; Liu, Y.; Ward, D.; Quan, J.; Ye, T.; Zhang, H. Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties. Cancer Res., 2011, 71(23), 7238-7249.
[87]
Wang, G.G.; Song, J.; Wang, Z.; Dormann, H.L.; Casadio, F.; Li, H.; Luo, J-L.; Patel, D.J.; Allis, C.D. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature, 2009, 459(7248), 847-851.
[88]
Reader, J.C.; Meekins, J.S.; Gojo, I.; Ning, Y. A novel NUP98-PHF23 fusion resulting from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia. Leukemia, 2007, 21(4), 842-844.
[89]
Gough, S.M.; Lee, F.; Yang, F.; Walker, R.L.; Zhu, Y.J.; Pineda, M.; Onozawa, M.; Chung, Y.J.; Bilke, S.; Wagner, E.K.; Denu, J.M.; Ning, Y.; Xu, B.; Wang, G.G.; Meltzer, P.S.; Aplan, P.D. NUP98-PHF23 is a chromatin-modifying oncoprotein that causes a wide array of leukemias sensitive to inhibition of PHD histone reader function. Cancer Discov., 2014, 4(5), 564-577.
[90]
Garkavtsev, I.; Kozin, S.V.; Chernova, O.; Xu, L.; Winkler, F.; Brown, E.; Barnett, G.H.; Jain, R.K. The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature, 2004, 428(6980), 328-332.
[91]
Thompson, B.; Townsley, F.; Rosin-Arbesfeld, R.; Musisi, H.; Bienz, M. A new nuclear component of the Wnt signalling pathway. Nat. Cell Biol., 2002, 4(5), 367-373.
[92]
Ceol, C.J.; Houvras, Y.; Jane-Valbuena, J.; Bilodeau, S.; Orlando, D.A.; Battisti, V.; Fritsch, L.; Lin, W.M.; Hollmann, T.J.; Ferré, F.; Bourque, C.; Burke, C.J.; Turner, L.; Uong, A.; Johnson, L.A.; Beroukhim, R.; Mermel, C.H.; Loda, M.; Ait-Si-Ali, S.; Garraway, L.A.; Young, R.A.; Zon, L.I. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature, 2011, 471(7339), 513-517.
[93]
Huang, J.; Dorsey, J.; Chuikov, S.; Pérez-Burgos, L.; Zhang, X.; Jenuwein, T.; Reinberg, D.; Berger, S.L. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J. Biol. Chem., 2010, 285(13), 9636-9641.
[94]
Chen, M.W.; Hua, K.T.; Kao, H.J.; Chi, C.C.; Wei, L.H.; Johansson, G.; Shiah, S.G.; Chen, P.S.; Jeng, Y.M.; Cheng, T.Y.; Lai, T.C.; Chang, J.S.; Jan, Y.H.; Chien, M.H.; Yang, C.J.; Huang, M.S.; Hsiao, M.; Kuo, M.L. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res., 2010, 70(20), 7830-7840.
[95]
Kubicek, S.; O’Sullivan, R.J.; August, E.M.; Hickey, E.R.; Zhang, Q.; Teodoro, M.L.; Rea, S.; Mechtler, K.; Kowalski, J.A.; Homon, C.A.; Kelly, T.A.; Jenuwein, T. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell, 2007, 25(3), 473-481.
[96]
Vedadi, M.; Barsyte-Lovejoy, D.; Liu, F.; Rival-Gervier, S.; Allali-Hassani, A.; Labrie, V.; Wigle, T.J.; Dimaggio, P.A.; Wasney, G.A.; Siarheyeva, A.; Dong, A.; Tempel, W.; Wang, S.C.; Chen, X.; Chau, I.; Mangano, T.J.; Huang, X.P.; Simpson, C.D.; Pattenden, S.G.; Norris, J.L.; Kireev, D.B.; Tripathy, A.; Edwards, A.; Roth, B.L.; Janzen, W.P.; Garcia, B.A.; Petronis, A.; Ellis, J.; Brown, P.J.; Frye, S.V.; Arrowsmith, C.H.; Jin, J. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat. Chem. Biol., 2011, 7(8), 566-574.
[97]
Rodriguez-Paredes, M.; Martinez de Paz, A.; Simó-Riudalbas, L.; Sayols, S.; Moutinho, C.; Moran, S.; Villanueva, A.; Vázquez-Cedeira, M.; Lazo, P.A.; Carneiro, F.; Moura, C.S.; Vieira, J.; Teixeira, M.R.; Esteller, M. Gene amplification of the histone methyltransferase SETDB1 contributes to human lung tumorigenesis. Oncogene, 2014, 33(21), 2807-2813.
[98]
Wu, P.C.; Lu, J.W.; Yang, J.Y.; Lin, I.H.; Ou, D.L.; Lin, Y.H.; Chou, K.H.; Huang, W.F.; Wang, W.P.; Huang, Y.L.; Hsu, C.; Lin, L.I.; Lin, Y.M.; Shen, C.K.; Tzeng, T.Y. H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. Cancer Res., 2014, 74(24), 7333-7343.
[99]
Fei, Q.; Shang, K.; Zhang, J.; Chuai, S.; Kong, D.; Zhou, T.; Fu, S.; Liang, Y.; Li, C.; Chen, Z.; Zhao, Y.; Yu, Z.; Huang, Z.; Hu, M.; Ying, H.; Chen, Z.; Zhang, Y.; Xing, F.; Zhu, J.; Xu, H.; Zhao, K.; Lu, C.; Atadja, P.; Xiao, Z.X.; Li, E.; Shou, J. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53. Nat. Commun., 2015, 6, 8651.
[100]
Sun, Q.Y.; Ding, L.W.; Xiao, J.F.; Chien, W.; Lim, S.L.; Hattori, N.; Goodglick, L.; Chia, D.; Mah, V.; Alavi, M.; Kim, S.R.; Doan, N.B.; Said, J.W.; Loh, X.Y.; Xu, L.; Liu, L.Z.; Yang, H.; Hayano, T.; Shi, S.; Xie, D.; Lin, D.C.; Koeffler, H.P. SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway. J. Pathol., 2015, 235(4), 559-570.
[101]
Wong, C.M.; Wei, L.; Law, C.T.; Ho, D.W.; Tsang, F.H.; Au, S.L.; Sze, K.M.; Lee, J.M.; Wong, C.C.; Ng, I.O. Up-regulation of histone methyltransferase SETDB1 by multiple mechanisms in hepatocellular carcinoma promotes cancer metastasis. Hepatology, 2016, 63(2), 474-487.
[102]
Peters, A.H.; O’Carroll, D.; Scherthan, H.; Mechtler, K.; Sauer, S.; Schöfer, C.; Weipoltshammer, K.; Pagani, M.; Lachner, M.; Kohlmaier, A.; Opravil, S.; Doyle, M.; Sibilia, M.; Jenuwein, T. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell, 2001, 107(3), 323-337.
[103]
Carbone, R.; Botrugno, O.A.; Ronzoni, S.; Insinga, A.; Di Croce, L.; Pelicci, P.G.; Minucci, S. Recruitment of the histone methyltransferase SUV39H1 and its role in the oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion protein. Mol. Cell. Biol., 2006, 26(4), 1288-1296.
[104]
Pogribny, I.P.; Ross, S.A.; Tryndyak, V.P.; Pogribna, M.; Poirier, L.A.; Karpinets, T.V. Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats. Carcinogenesis, 2006, 27(6), 1180-1186.
[105]
García-Cao, M.; O’Sullivan, R.; Peters, A.H.; Jenuwein, T.; Blasco, M.A. Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat. Genet., 2004, 36(1), 94-99.
[106]
Braig, M.; Lee, S.; Loddenkemper, C.; Rudolph, C.; Peters, A.H.; Schlegelberger, B.; Stein, H.; Dörken, B.; Jenuwein, T.; Schmitt, C.A. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature, 2005, 436(7051), 660-665.
[107]
Dong, C.; Wu, Y.; Wang, Y.; Wang, C.; Kang, T.; Rychahou, P.G.; Chi, Y.I.; Evers, B.M.; Zhou, B.P. Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer. Oncogene, 2013, 32(11), 1351-1362.
[108]
Lakshmikuttyamma, A.; Scott, S.A.; DeCoteau, J.F.; Geyer, C.R. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene, 2010, 29(4), 576-588.
[109]
Cherrier, T.; Suzanne, S.; Redel, L.; Calao, M.; Marban, C.; Samah, B.; Mukerjee, R.; Schwartz, C.; Gras, G.; Sawaya, B.E.; Zeichner, S.L.; Aunis, D.; Van Lint, C.; Rohr, O. p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1. Oncogene, 2009, 28(38), 3380-3389.
[110]
Zheng, Z.; Li, L.; Liu, X.; Wang, D.; Tu, B.; Wang, L.; Wang, H.; Zhu, W-G. 5-Aza-2′-deoxycytidine reactivates gene expression via degradation of pRb pocket proteins. FASEB J., 2012, 26(1), 449-459.
[111]
Björkman, M.; Östling, P.; Härmä, V.; Virtanen, J.; Mpindi, J.P.; Rantala, J.; Mirtti, T.; Vesterinen, T.; Lundin, M.; Sankila, A.; Rannikko, A.; Kaivanto, E.; Kohonen, P.; Kallioniemi, O.; Nees, M. Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion. Oncogene, 2012, 31(29), 3444-3456.
[112]
Cho, H.S.; Toyokawa, G.; Daigo, Y.; Hayami, S.; Masuda, K.; Ikawa, N.; Yamane, Y.; Maejima, K.; Tsunoda, T.; Field, H.I.; Kelly, J.D.; Neal, D.E.; Ponder, B.A.; Maehara, Y.; Nakamura, Y.; Hamamoto, R. The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. Int. J. Cancer, 2012, 131(3), E179-E189.
[113]
Ramadoss, S.; Sen, S.; Ramachandran, I.; Roy, S.; Chaudhuri, G.; Farias-Eisner, R. Lysine-specific demethylase KDM3A regulates ovarian cancer stemness and chemoresistance. Oncogene, 2016, 6(11), 1537-1545.
[114]
Parrish, J.K.; Sechler, M.; Winn, R.A.; Jedlicka, P. The histone demethylase KDM3A is a microRNA-22-regulated tumor promoter in Ewing Sarcoma. Oncogene, 2015, 34(2), 257-262.
[115]
Black, J.C.; Manning, A.L.; Van Rechem, C.; Kim, J.; Ladd, B.; Cho, J.; Pineda, C.M.; Murphy, N.; Daniels, D.L.; Montagna, C.; Lewis, P.W.; Glass, K.; Allis, C.D.; Dyson, N.J.; Getz, G.; Whetstine, J.R. KDM4A lysine demethylase induces site-specific copy gain and rereplication of regions amplified in tumors. Cell, 2013, 154(3), 541-555.
[116]
Wilson, C.; Qiu, L.; Hong, Y.; Karnik, T.; Tadros, G.; Mau, B.; Ma, T.; Mu, Y.; New, J.; Louie, R.J.; Gunewardena, S.; Godwin, A.K.; Tawfik, O.W.; Chien, J.; Roby, K.F.; Krieg, A.J. The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer. Oncogene, 2016, 36(18), 2565-2576.
[117]
Ye, Q.; Holowatyj, A.; Wu, J.; Liu, H.; Zhang, L.; Suzuki, T.; Yang, Z.Q. Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer. Am. J. Cancer Res., 2015, 5(4), 1519-1530.
[118]
Cheung, N.; Fung, T.K.; Zeisig, B.B.; Holmes, K.; Rane, J.K.; Mowen, K.A.; Finn, M.G.; Lenhard, B.; Chan, L.C.; So, C.W. Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia. Cancer Cell, 2016, 29(1), 32-48.
[119]
Osawa, T.; Tsuchida, R.; Muramatsu, M.; Shimamura, T.; Wang, F.; Suehiro, J.; Kanki, Y.; Wada, Y.; Yuasa, Y.; Aburatani, H.; Miyano, S.; Minami, T.; Kodama, T.; Shibuya, M. Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor-associated macrophages. Cancer Res., 2013, 73(10), 3019-3028.
[120]
Ramadoss, S.; Guo, G.; Wang, C.Y. Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53. Oncogene, 2017, 36(1), 47-59.
[121]
Martinez-Garcia, E.; Licht, J.D. Deregulation of H3K27 methylation in cancer. Nat. Genet., 2010, 42(2), 100-101.
[122]
Tamagawa, H.; Oshima, T.; Numata, M.; Yamamoto, N.; Shiozawa, M.; Morinaga, S.; Nakamura, Y.; Yoshihara, M.; Sakuma, Y.; Kameda, Y.; Akaike, M.; Yukawa, N.; Rino, Y.; Masuda, M.; Miyagi, Y. Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer. Eur. J. Surg. Oncol., 2013, 39(6), 655-661.
[123]
Mack, S.C.; Witt, H.; Piro, R.M.; Gu, L.; Zuyderduyn, S.; Stütz, A.M.; Wang, X.; Gallo, M.; Garzia, L.; Zayne, K.; Zhang, X.; Ramaswamy, V.; Jäger, N.; Jones, D.T.; Sill, M.; Pugh, T.J.; Ryzhova, M.; Wani, K.M.; Shih, D.J.; Head, R.; Remke, M.; Bailey, S.D.; Zichner, T.; Faria, C.C.; Barszczyk, M.; Stark, S.; Seker-Cin, H.; Hutter, S.; Johann, P.; Bender, S.; Hovestadt, V.; Tzaridis, T.; Dubuc, A.M.; Northcott, P.A.; Peacock, J.; Bertrand, K.C.; Agnihotri, S.; Cavalli, F.M.; Clarke, I.; Nethery-Brokx, K.; Creasy, C.L.; Verma, S.K.; Koster, J.; Wu, X.; Yao, Y.; Milde, T.; Sin-Chan, P.; Zuccaro, J.; Lau, L.; Pereira, S.; Castelo-Branco, P.; Hirst, M.; Marra, M.A.; Roberts, S.S.; Fults, D.; Massimi, L.; Cho, Y.J.; Van Meter, T.; Grajkowska, W.; Lach, B.; Kulozik, A.E.; von Deimling, A.; Witt, O.; Scherer, S.W.; Fan, X.; Muraszko, K.M.; Kool, M.; Pomeroy, S.L.; Gupta, N.; Phillips, J.; Huang, A.; Tabori, U.; Hawkins, C.; Malkin, D.; Kongkham, P.N.; Weiss, W.A.; Jabado, N.; Rutka, J.T.; Bouffet, E.; Korbel, J.O.; Lupien, M.; Aldape, K.D.; Bader, G.D.; Eils, R.; Lichter, P.; Dirks, P.B.; Pfister, S.M.; Korshunov, A.; Taylor, M.D. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature, 2014, 506(7489), 445-450.
[124]
Khuong-Quang, D.A.; Buczkowicz, P.; Rakopoulos, P.; Liu, X.Y.; Fontebasso, A.M.; Bouffet, E.; Bartels, U.; Albrecht, S.; Schwartzentruber, J.; Letourneau, L.; Bourgey, M.; Bourque, G.; Montpetit, A.; Bourret, G.; Lepage, P.; Fleming, A.; Lichter, P.; Kool, M.; von Deimling, A.; Sturm, D.; Korshunov, A.; Faury, D.; Jones, D.T.; Majewski, J.; Pfister, S.M.; Jabado, N.; Hawkins, C. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol., 2012, 124(3), 439-447.
[125]
Chan, K-M.; Fang, D.; Gan, H.; Hashizume, R.; Yu, C.; Schroeder, M.; Gupta, N.; Mueller, S.; James, C.D.; Jenkins, R.; Sarkaria, J.; Zhang, Z. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev., 2013, 27(9), 985-990.
[126]
Gielen, G.H.; Gessi, M.; Hammes, J.; Kramm, C.M.; Waha, A.; Pietsch, T. H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas. Am. J. Clin. Pathol., 2013, 139(3), 345-349.
[127]
Kleer, C.G.; Cao, Q.; Varambally, S.; Shen, R.; Ota, I.; Tomlins, S.A.; Ghosh, D.; Sewalt, R.G.; Otte, A.P.; Hayes, D.F.; Sabel, M.S.; Livant, D.; Weiss, S.J.; Rubin, M.A.; Chinnaiyan, A.M. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. USA, 2003, 100(20), 11606-11611.
[128]
Varambally, S.; Cao, Q.; Mani, R-S.; Shankar, S.; Wang, X.; Ateeq, B.; Laxman, B.; Cao, X.; Jing, X.; Ramnarayanan, K.; Brenner, J.C.; Yu, J.; Kim, J.H.; Han, B.; Tan, P.; Kumar-Sinha, C.; Lonigro, R.J.; Palanisamy, N.; Maher, C.A.; Chinnaiyan, A.M. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science, 2008, 322(5908), 1695-1699.
[129]
Sneeringer, C.J.; Scott, M.P.; Kuntz, K.W.; Knutson, S.K.; Pollock, R.M.; Richon, V.M.; Copeland, R.A. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc. Natl. Acad. Sci. USA, 2010, 107(49), 20980-20985.
[130]
Bödör, C.; Grossmann, V.; Popov, N.; Okosun, J.; O’Riain, C.; Tan, K.; Marzec, J.; Araf, S.; Wang, J.; Lee, A.M.; Clear, A.; Montoto, S.; Matthews, J.; Iqbal, S.; Rajnai, H.; Rosenwald, A.; Ott, G.; Campo, E.; Rimsza, L.M.; Smeland, E.B.; Chan, W.C.; Braziel, R.M.; Staudt, L.M.; Wright, G.; Lister, T.A.; Elemento, O.; Hills, R.; Gribben, J.G.; Chelala, C.; Matolcsy, A.; Kohlmann, A.; Haferlach, T.; Gascoyne, R.D.; Fitzgibbon, J. EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood, 2013, 122(18), 3165-3168.
[131]
Cao, Q.; Yu, J.; Dhanasekaran, S.M.; Kim, J.H.; Mani, R.S.; Tomlins, S.A.; Mehra, R.; Laxman, B.; Cao, X.; Yu, J.; Kleer, C.G.; Varambally, S.; Chinnaiyan, A.M. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene, 2008, 27(58), 7274-7284.
[132]
Wei, F.Z.; Cao, Z.; Wang, X.; Wang, H.; Cai, M.Y.; Li, T.; Hattori, N.; Wang, D.; Du, Y.; Song, B.; Cao, L.L.; Shen, C.; Wang, L.; Wang, H.; Yang, Y.; Xie, D.; Wang, F.; Ushijima, T.; Zhao, Y.; Zhu, W.G. Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway. Autophagy, 2015, 11(12), 2309-2322.
[133]
Bitler, B.G.; Aird, K.M.; Garipov, A.; Li, H.; Amatangelo, M.; Kossenkov, A.V.; Schultz, D.C.; Liu, Q.; Shih, IeM.; Conejo-Garcia, J.R.; Speicher, D.W.; Zhang, R. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat. Med., 2015, 21(3), 231-238.
[134]
Knutson, S.K.; Wigle, T.J.; Warholic, N.M.; Sneeringer, C.J.; Allain, C.J.; Klaus, C.R.; Sacks, J.D.; Raimondi, A.; Majer, C.R.; Song, J.; Scott, M.P.; Jin, L.; Smith, J.J.; Olhava, E.J.; Chesworth, R.; Moyer, M.P.; Richon, V.M.; Copeland, R.A.; Keilhack, H.; Pollock, R.M.; Kuntz, K.W. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat. Chem. Biol., 2012, 8(11), 890-896.
[135]
Kim, W.; Bird, G.H.; Neff, T.; Guo, G.; Kerenyi, M.A.; Walensky, L.D.; Orkin, S.H. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat. Chem. Biol., 2013, 9(10), 643-650.
[136]
Xiao, Z.G.; Shen, J.; Zhang, L.; Li, L.F.; Li, M.X.; Hu, W.; Li, Z.J.; Cho, C.H. The roles of histone demethylase UTX and JMJD3 (KDM6B) in cancers: current progress and future perspectives. Curr. Med. Chem., 2016, 23(32), 3687-3696.
[137]
Ntziachristos, P.; Tsirigos, A.; Welstead, G.G.; Trimarchi, T.; Bakogianni, S.; Xu, L.; Loizou, E.; Holmfeldt, L.; Strikoudis, A.; King, B.; Mullenders, J.; Becksfort, J.; Nedjic, J.; Paietta, E.; Tallman, M.S.; Rowe, J.M.; Tonon, G.; Satoh, T.; Kruidenier, L.; Prinjha, R.; Akira, S.; Van Vlierberghe, P.; Ferrando, A.A.; Jaenisch, R.; Mullighan, C.G.; Aifantis, I. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature, 2014, 514(7523), 513-517.
[138]
Anderton, J.A.; Bose, S.; Vockerodt, M.; Vrzalikova, K.; Wei, W.; Kuo, M.; Helin, K.; Christensen, J.; Rowe, M.; Murray, P.G.; Woodman, C.B. The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin’s lymphoma. Oncogene, 2011, 30(17), 2037-2043.
[139]
Tang, B.; Qi, G.; Tang, F.; Yuan, S.; Wang, Z.; Liang, X.; Li, B.; Yu, S.; Liu, J.; Huang, Q.; Wei, Y.; Zhai, R.; Lei, B.; Yu, H.; Tomlinson, S.; He, S. Aberrant JMJD3 expression upregulates slug to promote migration, invasion, and stem cell-like behaviors in hepatocellular carcinoma. Cancer Res., 2016, 76(22), 6520-6532.
[140]
van Haaften, G.; Dalgliesh, G.L.; Davies, H.; Chen, L.; Bignell, G.; Greenman, C.; Edkins, S.; Hardy, C.; O’Meara, S.; Teague, J.; Butler, A.; Hinton, J.; Latimer, C.; Andrews, J.; Barthorpe, S.; Beare, D.; Buck, G.; Campbell, P.J.; Cole, J.; Forbes, S.; Jia, M.; Jones, D.; Kok, C.Y.; Leroy, C.; Lin, M.L.; McBride, D.J.; Maddison, M.; Maquire, S.; McLay, K.; Menzies, A.; Mironenko, T.; Mulderrig, L.; Mudie, L.; Pleasance, E.; Shepherd, R.; Smith, R.; Stebbings, L.; Stephens, P.; Tang, G.; Tarpey, P.S.; Turner, R.; Turrell, K.; Varian, J.; West, S.; Widaa, S.; Wray, P.; Collins, V.P.; Ichimura, K.; Law, S.; Wong, J.; Yuen, S.T.; Leung, S.Y.; Tonon, G.; DePinho, R.A.; Tai, Y.T.; Anderson, K.C.; Kahnoski, R.J.; Massie, A.; Khoo, S.K.; Teh, B.T.; Stratton, M.R.; Futreal, P.A. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat. Genet., 2009, 41(5), 521-523.
[141]
Fang, D.; Gan, H.; Lee, J.H.; Han, J.; Wang, Z.; Riester, S.M.; Jin, L.; Chen, J.; Zhou, H.; Wang, J.; Zhang, H.; Yang, N.; Bradley, E.W.; Ho, T.H.; Rubin, B.P.; Bridge, J.A.; Thibodeau, S.N.; Ordog, T.; Chen, Y.; van Wijnen, A.J.; Oliveira, A.M.; Xu, R.M.; Westendorf, J.J.; Zhang, Z. The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas. Science, 2016, 352(6291), 1344-1348.
[142]
Lu, C.; Jain, S.U.; Hoelper, D.; Bechet, D.; Molden, R.C.; Ran, L.; Murphy, D.; Venneti, S.; Hameed, M.; Pawel, B.R.; Wunder, J.S.; Dickson, B.C.; Lundgren, S.M.; Jani, K.S.; De Jay, N.; Papillon-Cavanagh, S.; Andrulis, I.L.; Sawyer, S.L.; Grynspan, D.; Turcotte, R.E.; Nadaf, J.; Fahiminiyah, S.; Muir, T.W.; Majewski, J.; Thompson, C.B.; Chi, P.; Garcia, B.A.; Allis, C.D.; Jabado, N.; Lewis, P.W. Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape. Science, 2016, 352(6287), 844-849.
[143]
Papillon-Cavanagh, S.; Lu, C.; Gayden, T.; Mikael, L.G.; Bechet, D.; Karamboulas, C.; Ailles, L.; Karamchandani, J.; Marchione, D.M.; Garcia, B.A.; Weinreb, I.; Goldstein, D.; Lewis, P.W.; Dancu, O.M.; Dhaliwal, S.; Stecho, W.; Howlett, C.J.; Mymryk, J.S.; Barrett, J.W.; Nichols, A.C.; Allis, C.D.; Majewski, J.; Jabado, N. Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas. Nat. Genet., 2017, 49(2), 180-185.
[144]
Jaju, R.J.; Fidler, C.; Haas, O.A.; Strickson, A.J.; Watkins, F.; Clark, K.; Cross, N.C.; Cheng, J-F.; Aplan, P.D.; Kearney, L.; Boultwood, J.; Wainscoat, J.S. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood, 2001, 98(4), 1264-1267.
[145]
Chesi, M.; Nardini, E.; Lim, R.S.; Smith, K.D.; Kuehl, W.M.; Bergsagel, P.L. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood, 1998, 92(9), 3025-3034.
[146]
Martinez-Garcia, E.; Popovic, R.; Min, D-J.; Sweet, S.M.; Thomas, P.M.; Zamdborg, L.; Heffner, A.; Will, C.; Lamy, L.; Staudt, L.M.; Levens, D.L.; Kelleher, N.L.; Licht, J.D. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood, 2011, 117(1), 211-220.
[147]
Zhu, X.; He, F.; Zeng, H.; Ling, S.; Chen, A.; Wang, Y.; Yan, X.; Wei, W.; Pang, Y.; Cheng, H.; Hua, C.; Zhang, Y.; Yang, X.; Lu, X.; Cao, L.; Hao, L.; Dong, L.; Zou, W.; Wu, J.; Li, X.; Zheng, S.; Yan, J.; Zhou, J.; Zhang, L.; Mi, S.; Wang, X.; Zhang, L.; Zou, Y.; Chen, Y.; Geng, Z.; Wang, J.; Zhou, J.; Liu, X.; Wang, J.; Yuan, W.; Huang, G.; Cheng, T.; Wang, Q.F. Identification of functional cooperative mutations of SETD2 in human acute leukemia. Nat. Genet., 2014, 46(3), 287-293.
[148]
Fontebasso, A.M.; Schwartzentruber, J.; Khuong-Quang, D-A.; Liu, X-Y.; Sturm, D.; Korshunov, A.; Jones, D.T.; Witt, H.; Kool, M.; Albrecht, S.; Fleming, A.; Hadjadj, D.; Busche, S.; Lepage, P.; Montpetit, A.; Staffa, A.; Gerges, N.; Zakrzewska, M.; Zakrzewski, K.; Liberski, P.P.; Hauser, P.; Garami, M.; Klekner, A.; Bognar, L.; Zadeh, G.; Faury, D.; Pfister, S.M.; Jabado, N.; Majewski, J. Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas. Acta Neuropathol., 2013, 125(5), 659-669.
[149]
Parker, H.; Rose-Zerilli, M.J.; Larrayoz, M.; Clifford, R.; Edelmann, J.; Blakemore, S.; Gibson, J.; Wang, J.; Ljungström, V.; Wojdacz, T.K.; Chaplin, T.; Roghanian, A.; Davis, Z.; Parker, A.; Tausch, E.; Ntoufa, S.; Ramos, S.; Robbe, P.; Alsolami, R.; Steele, A.J.; Packham, G.; Rodríguez-Vicente, A.E.; Brown, L.; McNicholl, F.; Forconi, F.; Pettitt, A.; Hillmen, P.; Dyer, M.; Cragg, M.S.; Chelala, C.; Oakes, C.C.; Rosenquist, R.; Stamatopoulos, K.; Stilgenbauer, S.; Knight, S.; Schuh, A.; Oscier, D.G.; Strefford, J.C. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia. Leukemia, 2016, 30(11), 2179-2186.
[150]
Duns, G.; van den Berg, E.; van Duivenbode, I.; Osinga, J.; Hollema, H.; Hofstra, R.M.; Kok, K. Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Res., 2010, 70(11), 4287-4291.
[151]
Newbold, R.F.; Mokbel, K. Evidence for a tumour suppressor function of SETD2 in human breast cancer: a new hypothesis. Anticancer Res., 2010, 30(9), 3309-3311.
[152]
Jaffe, J.D.; Wang, Y.; Chan, H.M.; Zhang, J.; Huether, R.; Kryukov, G.V.; Bhang, H.E.; Taylor, J.E.; Hu, M.; Englund, N.P.; Yan, F.; Wang, Z.; Robert McDonald, E., III; Wei, L.; Ma, J.; Easton, J.; Yu, Z.; deBeaumount, R.; Gibaja, V.; Venkatesan, K.; Schlegel, R.; Sellers, W.R.; Keen, N.; Liu, J.; Caponigro, G.; Barretina, J.; Cooke, V.G.; Mullighan, C.; Carr, S.A.; Downing, J.R.; Garraway, L.A.; Stegmeier, F. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat. Genet., 2013, 45(11), 1386-1391.
[153]
Oyer, J.A.; Huang, X.; Zheng, Y.; Shim, J.; Ezponda, T.; Carpenter, Z.; Allegretta, M.; Okot-Kotber, C.I.; Patel, J.P.; Melnick, A.; Levine, R.L.; Ferrando, A.; Mackerell, A.D., Jr; Kelleher, N.L.; Licht, J.D.; Popovic, R. Point mutation E1099K in MMSET/NSD2 enhances its methyltranferase activity and leads to altered global chromatin methylation in lymphoid malignancies. Leukemia, 2014, 28(1), 198-201.
[154]
Tzatsos, A.; Paskaleva, P.; Ferrari, F.; Deshpande, V.; Stoykova, S.; Contino, G.; Wong, K.K.; Lan, F.; Trojer, P.; Park, P.J.; Bardeesy, N. KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. J. Clin. Invest., 2013, 123(2), 727-739.
[155]
He, J.; Nguyen, A.T.; Zhang, Y. KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia. Blood, 2011, 117(14), 3869-3880.
[156]
Andricovich, J.; Kai, Y.; Peng, W.; Foudi, A.; Tzatsos, A. Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis. J. Clin. Invest., 2016, 126(3), 905-920.
[157]
Wagner, K.W.; Alam, H.; Dhar, S.S.; Giri, U.; Li, N.; Wei, Y.; Giri, D.; Cascone, T.; Kim, J.H.; Ye, Y.; Multani, A.S.; Chan, C.H.; Erez, B.; Saigal, B.; Chung, J.; Lin, H.K.; Wu, X.; Hung, M.C.; Heymach, J.V.; Lee, M.G. KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. J. Clin. Invest., 2013, 123(12), 5231-5246.
[158]
Dhar, S.S.; Alam, H.; Li, N.; Wagner, K.W.; Chung, J.; Ahn, Y.W.; Lee, M.G. Transcriptional repression of histone deacetylase 3 by the histone demethylase KDM2A is coupled to tumorigenicity of lung cancer cells. J. Biol. Chem., 2014, 289(11), 7483-7496.
[159]
Cao, L.L.; Wei, F.; Du, Y.; Song, B.; Wang, D.; Shen, C.; Lu, X.; Cao, Z.; Yang, Q.; Gao, Y.; Wang, L.; Zhao, Y.; Wang, H.; Yang, Y.; Zhu, W.G. ATM-mediated KDM2A phosphorylation is required for the DNA damage repair. Oncogene, 2016, 35(3), 301-313.
[160]
Okada, Y.; Feng, Q.; Lin, Y.; Jiang, Q.; Li, Y.; Coffield, V.M.; Su, L.; Xu, G.; Zhang, Y. hDOT1L links histone methylation to leukemogenesis. Cell, 2005, 121(2), 167-178.
[161]
Okada, Y.; Jiang, Q.; Lemieux, M.; Jeannotte, L.; Su, L.; Zhang, Y. Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat. Cell Biol., 2006, 8(9), 1017-1024.
[162]
Bernt, K.M.; Zhu, N.; Sinha, A.U.; Vempati, S.; Faber, J.; Krivtsov, A.V.; Feng, Z.; Punt, N.; Daigle, A.; Bullinger, L.; Pollock, R.M.; Richon, V.M.; Kung, A.L.; Armstrong, S.A. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell, 2011, 20(1), 66-78.
[163]
Krivtsov, A.V.; Feng, Z.; Lemieux, M.E.; Faber, J.; Vempati, S.; Sinha, A.U.; Xia, X.; Jesneck, J.; Bracken, A.P.; Silverman, L.B.; Kutok, J.L.; Kung, A.L.; Armstrong, S.A. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell, 2008, 14(5), 355-368.
[164]
Lin, Y.H.; Kakadia, P.M.; Chen, Y.; Li, Y.Q.; Deshpande, A.J.; Buske, C.; Zhang, K.L.; Zhang, Y.; Xu, G.L.; Bohlander, S.K. Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias. Blood, 2009, 114(3), 651-658.
[165]
Chen, C.W.; Koche, R.P.; Sinha, A.U.; Deshpande, A.J.; Zhu, N.; Eng, R.; Doench, J.G.; Xu, H.; Chu, S.H.; Qi, J.; Wang, X.; Delaney, C.; Bernt, K.M.; Root, D.E.; Hahn, W.C.; Bradner, J.E.; Armstrong, S.A. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat. Med., 2015, 21(4), 335-343.
[166]
Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Majer, C.R.; Sneeringer, C.J.; Song, J.; Johnston, L.D.; Scott, M.P.; Smith, J.J.; Xiao, Y.; Jin, L.; Kuntz, K.W.; Chesworth, R.; Moyer, M.P.; Bernt, K.M.; Tseng, J.C.; Kung, A.L.; Armstrong, S.A.; Copeland, R.A.; Richon, V.M.; Pollock, R.M. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell, 2011, 20(1), 53-65.
[167]
Kim, W.; Kim, R.; Park, G.; Park, J.W.; Kim, J.E. Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation. J. Biol. Chem., 2012, 287(8), 5588-5599.
[168]
Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Basavapathruni, A.; Jin, L.; Boriack-Sjodin, P.A.; Allain, C.J.; Klaus, C.R.; Raimondi, A.; Scott, M.P.; Waters, N.J.; Chesworth, R.; Moyer, M.P.; Copeland, R.A.; Richon, V.M.; Pollock, R.M. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood, 2013, 122(6), 1017-1025.
[169]
Rau, R.E.; Rodriguez, B.A.; Luo, M.; Jeong, M.; Rosen, A.; Rogers, J.H.; Campbell, C.T.; Daigle, S.R.; Deng, L.; Song, Y.; Sweet, S.; Chevassut, T.; Andreeff, M.; Kornblau, S.M.; Li, W.; Goodell, M.A. DOT1L as a therapeutic target for the treatment of DNMT3A-mutant acute myeloid leukemia. Blood, 2016, 128(7), 971-981.
[170]
Kerry, J.; Godfrey, L.; Repapi, E.; Tapia, M.; Blackledge, N.P.; Ma, H.; Ballabio, E.; O’Byrne, S.; Ponthan, F.; Heidenreich, O.; Roy, A.; Roberts, I.; Konopleva, M.; Klose, R.J.; Geng, H.; Milne, T.A. MLL-AF4 spreading identifies binding sites that are distinct from super-enhancers and that govern sensitivity to DOT1L inhibition in leukemia. Cell Reports, 2017, 18(2), 482-495.
[171]
Schneider, A.C.; Heukamp, L.C.; Rogenhofer, S.; Fechner, G.; Bastian, P.J.; von Ruecker, A.; Müller, S.C.; Ellinger, J. Global histone H4K20 trimethylation predicts cancer-specific survival in patients with muscle-invasive bladder cancer. BJU Int., 2011, 108(2), E290-E296.
[172]
Yokoyama, Y.; Matsumoto, A.; Hieda, M.; Shinchi, Y.; Ogihara, E.; Hamada, M.; Nishioka, Y.; Kimura, H.; Yoshidome, K.; Tsujimoto, M.; Matsuura, N. Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity. Breast Cancer Res., 2014, 16(3), R66.
[173]
Behbahani, T.E.; Kahl, P.; von der Gathen, J.; Heukamp, L.C.; Baumann, C.; Gütgemann, I.; Walter, B.; Hofstädter, F.; Bastian, P.J.; von Ruecker, A.; Müller, S.C.; Rogenhofer, S.; Ellinger, J. Alterations of global histone H4K20 methylation during prostate carcinogenesis. BMC Urol., 2012, 12(1), 5.
[174]
Tryndyak, V.P.; Kovalchuk, O.; Pogribny, I.P. Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Cancer Biol. Ther., 2006, 5(1), 65-70.
[175]
Benetti, R.; Gonzalo, S.; Jaco, I.; Schotta, G.; Klatt, P.; Jenuwein, T.; Blasco, M.A. Suv4-20h deficiency results in telomere elongation and derepression of telomere recombination. J. Cell Biol., 2007, 178(6), 925-936.
[176]
Shinchi, Y.; Hieda, M.; Nishioka, Y.; Matsumoto, A.; Yokoyama, Y.; Kimura, H.; Matsuura, S.; Matsuura, N. SUV420H2 suppresses breast cancer cell invasion through down regulation of the SH2 domain-containing focal adhesion protein tensin-3. Exp. Cell Res., 2015, 334(1), 90-99.
[177]
Song, F.; Zheng, H.; Liu, B.; Wei, S.; Dai, H.; Zhang, L.; Calin, G.A.; Hao, X.; Wei, Q.; Zhang, W.; Chen, K. An miR-502-binding site single-nucleotide polymorphism in the 3′-untranslated region of the SET8 gene is associated with early age of breast cancer onset. Clin. Cancer Res., 2009, 15(19), 6292-6300.
[178]
Yang, F.; Sun, L.; Li, Q.; Han, X.; Lei, L.; Zhang, H.; Shang, Y. SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities. EMBO J., 2012, 31(1), 110-123.
[179]
Hou, L.; Li, Q.; Yu, Y.; Li, M.; Zhang, D. SET8 induces epithelial-mesenchymal transition and enhances prostate cancer cell metastasis by cooperating with ZEB1. Mol. Med. Rep., 2016, 13(2), 1681-1688.
[180]
Nikolaou, K.C.; Moulos, P.; Chalepakis, G.; Hatzis, P.; Oda, H.; Reinberg, D.; Talianidis, I. Spontaneous development of hepatocellular carcinoma with cancer stem cell properties in PR-SET7-deficient livers. EMBO J., 2015, 34(4), 430-447.
[181]
Yang, Y.; Bedford, M.T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer, 2013, 13(1), 37-50.
[182]
Cheung, N.; Chan, L.C.; Thompson, A.; Cleary, M.L.; So, C.W. Protein arginine-methyltransferase-dependent oncogenesis. Nat. Cell Biol., 2007, 9(10), 1208-1215.
[183]
Pal, S.; Baiocchi, R.A.; Byrd, J.C.; Grever, M.R.; Jacob, S.T.; Sif, S. Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J., 2007, 26(15), 3558-3569.
[184]
Aggarwal, P.; Vaites, L.P.; Kim, J.K.; Mellert, H.; Gurung, B.; Nakagawa, H.; Herlyn, M.; Hua, X.; Rustgi, A.K.; McMahon, S.B.; Diehl, J.A. Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell, 2010, 18(4), 329-340.
[185]
Chan-Penebre, E.; Kuplast, K.G.; Majer, C.R.; Boriack-Sjodin, P.A.; Wigle, T.J.; Johnston, L.D.; Rioux, N.; Munchhof, M.J.; Jin, L.; Jacques, S.L.; West, K.A.; Lingaraj, T.; Stickland, K.; Ribich, S.A.; Raimondi, A.; Scott, M.P.; Waters, N.J.; Pollock, R.M.; Smith, J.J.; Barbash, O.; Pappalardi, M.; Ho, T.F.; Nurse, K.; Oza, K.P.; Gallagher, K.T.; Kruger, R.; Moyer, M.P.; Copeland, R.A.; Chesworth, R.; Duncan, K.W. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat. Chem. Biol., 2015, 11(6), 432-437.
[186]
Chen, H.; Lorton, B.; Gupta, V.; Shechter, D.A. TGFbeta-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene, 2016, 36(3), 373-386.
[187]
Yao, R.; Jiang, H.; Ma, Y.; Wang, L.; Wang, L.; Du, J.; Hou, P.; Gao, Y.; Zhao, L.; Wang, G.; Zhang, Y.; Liu, D.X.; Huang, B.; Lu, J. PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. Cancer Res., 2014, 74(19), 5656-5667.
[188]
Banáth, J.P.; Macphail, S.H.; Olive, P.L. Radiation sensitivity, H2AX phosphorylation, and kinetics of repair of DNA strand breaks in irradiated cervical cancer cell lines. Cancer Res., 2004, 64(19), 7144-7149.
[189]
Sedelnikova, O.A.; Bonner, W.M. GammaH2AX in cancer cells: a potential biomarker for cancer diagnostics, prediction and recurrence. Cell Cycle, 2006, 5(24), 2909-2913.
[190]
Spring, K.; Ahangari, F.; Scott, S.P.; Waring, P.; Purdie, D.M.; Chen, P.C.; Hourigan, K.; Ramsay, J.; McKinnon, P.J.; Swift, M.; Lavin, M.F. Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. Nat. Genet., 2002, 32(1), 185-190.
[191]
Renwick, A.; Thompson, D.; Seal, S.; Kelly, P.; Chagtai, T.; Ahmed, M.; North, B.; Jayatilake, H.; Barfoot, R.; Spanova, K.; McGuffog, L.; Evans, D.G.; Eccles, D.; Easton, D.F.; Stratton, M.R.; Rahman, N. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat. Genet., 2006, 38(8), 873-875.
[192]
Sarkaria, J.N.; Busby, E.C.; Tibbetts, R.S.; Roos, P.; Taya, Y.; Karnitz, L.M.; Abraham, R.T. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res., 1999, 59(17), 4375-4382.
[193]
Munck, J.M.; Batey, M.A.; Zhao, Y.; Jenkins, H.; Richardson, C.J.; Cano, C.; Tavecchio, M.; Barbeau, J.; Bardos, J.; Cornell, L.; Griffin, R.J.; Menear, K.; Slade, A.; Thommes, P.; Martin, N.M.; Newell, D.R.; Smith, G.C.; Curtin, N.J. Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol. Cancer Ther., 2012, 11(8), 1789-1798.
[194]
James, C.; Ugo, V.; Le Couédic, J-P.; Staerk, J.; Delhommeau, F.; Lacout, C.; Garçon, L.; Raslova, H.; Berger, R.; Bennaceur-Griscelli, A.; Villeval, J.L.; Constantinescu, S.N.; Casadevall, N.; Vainchenker, W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature, 2005, 434(7037), 1144-1148.
[195]
Jelinek, J.; Oki, Y.; Gharibyan, V.; Bueso-Ramos, C.; Prchal, J.T.; Verstovsek, S.; Beran, M.; Estey, E.; Kantarjian, H.M.; Issa, J-P.J. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood, 2005, 106(10), 3370-3373.
[196]
Levine, R.L.; Wadleigh, M.; Cools, J.; Ebert, B.L.; Wernig, G.; Huntly, B.J.; Boggon, T.J.; Wlodarska, I.; Clark, J.J.; Moore, S.; Adelsperger, J.; Koo, S.; Lee, J.C.; Gabriel, S.; Mercher, T.; D’Andrea, A.; Fröhling, S.; Döhner, K.; Marynen, P.; Vandenberghe, P.; Mesa, R.A.; Tefferi, A.; Griffin, J.D.; Eck, M.J.; Sellers, W.R.; Meyerson, M.; Golub, T.R.; Lee, S.J.; Gilliland, D.G. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell, 2005, 7(4), 387-397.
[197]
Baxter, E.J.; Scott, L.M.; Campbell, P.J.; East, C.; Fourouclas, N.; Swanton, S.; Vassiliou, G.S.; Bench, A.J.; Boyd, E.M.; Curtin, N.; Scott, M.A.; Erber, W.N.; Green, A.R. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 2005, 365(9464), 1054-1061.
[198]
Kralovics, R.; Passamonti, F.; Buser, A.S.; Teo, S.S.; Tiedt, R.; Passweg, J.R.; Tichelli, A.; Cazzola, M.; Skoda, R.C. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med., 2005, 352(17), 1779-1790.
[199]
Dawson, M.A.; Bannister, A.J.; Göttgens, B.; Foster, S.D.; Bartke, T.; Green, A.R.; Kouzarides, T. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature, 2009, 461(7265), 819-822.
[200]
Hedvat, M.; Huszar, D.; Herrmann, A.; Gozgit, J.M.; Schroeder, A.; Sheehy, A.; Buettner, R.; Proia, D.; Kowolik, C.M.; Xin, H.; Armstrong, B.; Bebernitz, G.; Weng, S.; Wang, L.; Ye, M.; McEachern, K.; Chen, H.; Morosini, D.; Bell, K.; Alimzhanov, M.; Ioannidis, S.; McCoon, P.; Cao, Z.A.; Yu, H.; Jove, R.; Zinda, M. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell, 2009, 16(6), 487-497.
[201]
Meydan, N.; Grunberger, T.; Dadi, H.; Shahar, M.; Arpaia, E.; Lapidot, Z.; Leeder, J.S.; Freedman, M.; Cohen, A.; Gazit, A.; Levitzki, A.; Roifman, C.M. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature, 1996, 379(6566), 645-648.
[202]
Bischoff, J.R.; Anderson, L.; Zhu, Y.; Mossie, K.; Ng, L.; Souza, B.; Schryver, B.; Flanagan, P.; Clairvoyant, F.; Ginther, C.; Chan, C.S.; Novotny, M.; Slamon, D.J.; Plowman, G.D. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J., 1998, 17(11), 3052-3065.
[203]
Li, D.; Zhu, J.; Firozi, P.F.; Abbruzzese, J.L.; Evans, D.B.; Cleary, K.; Friess, H.; Sen, S. Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin. Cancer Res., 2003, 9(3), 991-997.
[204]
Lens, S.M.; Voest, E.E.; Medema, R.H. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat. Rev. Cancer, 2010, 10(12), 825-841.
[205]
Katayama, H.; Sasai, K.; Kawai, H.; Yuan, Z-M.; Bondaruk, J.; Suzuki, F.; Fujii, S.; Arlinghaus, R.B.; Czerniak, B.A.; Sen, S. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat. Genet., 2004, 36(1), 55-62.
[206]
Hirota, T.; Lipp, J.J.; Toh, B-H.; Peters, J-M. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature, 2005, 438(7071), 1176-1180.
[207]
Amson, R.; Sigaux, F.; Przedborski, S.; Flandrin, G.; Givol, D.; Telerman, A. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias. Proc. Natl. Acad. Sci. USA, 1989, 86(22), 8857-8861.
[208]
van Lohuizen, M.; Verbeek, S.; Krimpenfort, P.; Domen, J.; Saris, C.; Radaszkiewicz, T.; Berns, A. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell, 1989, 56(4), 673-682.
[209]
Brasó-Maristany, F.; Filosto, S.; Catchpole, S.; Marlow, R.; Quist, J.; Francesch-Domenech, E.; Plumb, D.A.; Zakka, L.; Gazinska, P.; Liccardi, G.; Meier, P.; Gris-Oliver, A.; Cheang, M.C.; Perdrix-Rosell, A.; Shafat, M.; Noël, E.; Patel, N.; McEachern, K.; Scaltriti, M.; Castel, P.; Noor, F.; Buus, R.; Mathew, S.; Watkins, J.; Serra, V.; Marra, P.; Grigoriadis, A.; Tutt, A.N. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat. Med., 2016, 22(11), 1303-1313.
[210]
Zippo, A.; De Robertis, A.; Serafini, R.; Oliviero, S. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat. Cell Biol., 2007, 9(8), 932-944.
[211]
Harrington, E.A.; Bebbington, D.; Moore, J.; Rasmussen, R.K.; Ajose-Adeogun, A.O.; Nakayama, T.; Graham, J.A.; Demur, C.; Hercend, T.; Diu-Hercend, A.; Su, M.; Golec, J.M.; Miller, K.M. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med., 2004, 10(3), 262-267.
[212]
Carvajal, R.D.; Tse, A.; Schwartz, G.K. Aurora kinases: new targets for cancer therapy. Clin. Cancer Res., 2006, 12(23), 6869-6875.
[213]
Horiuchi, D.; Camarda, R.; Zhou, A.Y.; Yau, C.; Momcilovic, O.; Balakrishnan, S.; Corella, A.N.; Eyob, H.; Kessenbrock, K.; Lawson, D.A.; Marsh, L.A.; Anderton, B.N.; Rohrberg, J.; Kunder, R.; Bazarov, A.V.; Yaswen, P.; McManus, M.T.; Rugo, H.S.; Werb, Z.; Goga, A. PIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression. Nat. Med., 2016, 22(11), 1321-1329.
[214]
Li, J.; Yen, C.; Liaw, D.; Podsypanina, K.; Bose, S.; Wang, S.I.; Puc, J.; Miliaresis, C.; Rodgers, L.; McCombie, R.; Bigner, S.H.; Giovanella, B.C.; Ittmann, M.; Tycko, B.; Hibshoosh, H.; Wigler, M.H.; Parsons, R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308), 1943-1947.
[215]
Chen, W.; Possemato, R.; Campbell, K.T.; Plattner, C.A.; Pallas, D.C.; Hahn, W.C. Identification of specific PP2A complexes involved in human cell transformation. Cancer Cell, 2004, 5(2), 127-136.
[216]
Seshacharyulu, P.; Pandey, P.; Datta, K.; Batra, S.K. Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett., 2013, 335(1), 9-18.
[217]
Mailand, N.; Bekker-Jensen, S.; Faustrup, H.; Melander, F.; Bartek, J.; Lukas, C.; Lukas, J. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell, 2007, 131(5), 887-900.
[218]
Lee, H.J.; Li, C.F.; Ruan, D.; Powers, S.; Thompson, P.A.; Frohman, M.A.; Chan, C.H. The DNA damage transducer RNF8 facilitates cancer chemoresistance and progression through Twist activation. Mol. Cell, 2016, 63(6), 1021-1033.
[219]
Mattiroli, F.; Vissers, J.H.; van Dijk, W.J.; Ikpa, P.; Citterio, E.; Vermeulen, W.; Marteijn, J.A.; Sixma, T.K. RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell, 2012, 150(6), 1182-1195.
[220]
Chroma, K.; Mistrik, M.; Moudry, P.; Gursky, J.; Liptay, M.; Strauss, R.; Skrott, Z.; Vrtel, R.; Bartkova, J.; Kramara, J.; Bartek, J. Tumors overexpressing RNF168 show altered DNA repair and responses to genotoxic treatments, genomic instability and resistance to proteotoxic stress. Oncogene, 2016, 36(17), 2405-2422.
[221]
Wang, Y.; Zhang, N.; Zhang, L.; Li, R.; Fu, W.; Ma, K.; Li, X.; Wang, L.; Wang, J.; Zhang, H.; Gu, W.; Zhu, W.G.; Zhao, Y. Autophagy regulates chromatin ubiquitination in DNA damage response through elimination of SQSTM1/p62. Mol. Cell, 2016, 63(1), 34-48.
[222]
Koutelou, E.; Hirsch, C.L.; Dent, S.Y. Multiple faces of the SAGA complex. Curr. Opin. Cell Biol., 2010, 22(3), 374-382.
[223]
Zhang, X.Y.; Varthi, M.; Sykes, S.M.; Phillips, C.; Warzecha, C.; Zhu, W.; Wyce, A.; Thorne, A.W.; Berger, S.L.; McMahon, S.B. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol. Cell, 2008, 29(1), 102-111.
[224]
Atanassov, B.S.; Mohan, R.D.; Lan, X.; Kuang, X.; Lu, Y.; Lin, K.; McIvor, E.; Li, W.; Zhang, Y.; Florens, L.; Byrum, S.D.; Mackintosh, S.G.; Calhoun-Davis, T.; Koutelou, E.; Wang, L.; Tang, D.G.; Tackett, A.J.; Washburn, M.P.; Workman, J.L.; Dent, S.Y. ATXN7L3 and ENY2 coordinate activity of multiple H2B deubiquitinases important for cellular proliferation and tumor growth. Mol. Cell, 2016, 62(4), 558-571.
[225]
Gu, Y.; Jones, A.E.; Yang, W.; Liu, S.; Dai, Q.; Liu, Y.; Swindle, C.S.; Zhou, D.; Zhang, Z.; Ryan, T.M.; Townes, T.M.; Klug, C.A.; Chen, D.; Wang, H. The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function. Proc. Natl. Acad. Sci. USA, 2016, 113(1), E51-E60.
[226]
Wang, E.; Kawaoka, S.; Yu, M.; Shi, J.; Ni, T.; Yang, W.; Zhu, J.; Roeder, R.G.; Vakoc, C.R. Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia. Proc. Natl. Acad. Sci. USA, 2013, 110(10), 3901-3906.
[227]
Tarcic, O.; Pateras, I.S.; Cooks, T.; Shema, E.; Kanterman, J.; Ashkenazi, H.; Boocholez, H.; Hubert, A.; Rotkopf, R.; Baniyash, M.; Pikarsky, E.; Gorgoulis, V.G.; Oren, M. RNF20 links histone H2B ubiquitylation with inflammation and inflammation-associated cancer. Cell Reports, 2016, 14(6), 1462-1476.
[228]
Wang, Z.Q.; Stingl, L.; Morrison, C.; Jantsch, M.; Los, M.; Schulze-Osthoff, K.; Wagner, E.F. PARP is important for genomic stability but dispensable in apoptosis. Genes Dev., 1997, 11(18), 2347-2358.
[229]
Simbulan-Rosenthal, C.M.; Haddad, B.R.; Rosenthal, D.S.; Weaver, Z.; Coleman, A.; Luo, R.; Young, H.M.; Wang, Z.Q.; Ried, T.; Smulson, M.E. Chromosomal aberrations in PARP(-/-) mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc. Natl. Acad. Sci. USA, 1999, 96(23), 13191-13196.
[230]
Bryant, H.E.; Schultz, N.; Thomas, H.D.; Parker, K.M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N.J.; Helleday, T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 2005, 434(7035), 913-917.
[231]
de Murcia, J.M.; Niedergang, C.; Trucco, C.; Ricoul, M.; Dutrillaux, B.; Mark, M.; Oliver, F.J.; Masson, M.; Dierich, A.; LeMeur, M.; Walztinger, C.; Chambon, P.; de Murcia, G. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc. Natl. Acad. Sci. USA, 1997, 94(14), 7303-7307.
[232]
Ellisen, L.W. PARP inhibitors in cancer therapy: promise, progress, and puzzles. Cancer Cell, 2011, 19(2), 165-167.
[233]
Pommier, Y.; O’Connor, M.J.; de Bono, J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci. Transl. Med., 2016, 8(362), 362ps17.
[234]
Esposito, M.T.; Zhao, L.; Fung, T.K.; Rane, J.K.; Wilson, A.; Martin, N.; Gil, J.; Leung, A.Y.; Ashworth, A.; So, C.W. Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors. Nat. Med., 2015, 21(12), 1481-1490.
[235]
Du, Y.; Yamaguchi, H.; Wei, Y.; Hsu, J.L.; Wang, H.L.; Hsu, Y.H.; Lin, W.C.; Yu, W.H.; Leonard, P.G.; Lee, G.R., IV; Chen, M.K.; Nakai, K.; Hsu, M.C.; Chen, C.T.; Sun, Y.; Wu, Y.; Chang, W.C.; Huang, W.C.; Liu, C.L.; Chang, Y.C.; Chen, C.H.; Park, M.; Jones, P.; Hortobagyi, G.N.; Hung, M.C. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors. Nat. Med., 2016, 22(2), 194-201.
[236]
Huang, X.; Motea, E.A.; Moore, Z.R.; Yao, J.; Dong, Y.; Chakrabarti, G.; Kilgore, J.A.; Silvers, M.A.; Patidar, P.L.; Cholka, A.; Fattah, F.; Cha, Y.; Anderson, G.G.; Kusko, R.; Peyton, M.; Yan, J.; Xie, X.J.; Sarode, V.; Williams, N.S.; Minna, J.D.; Beg, M.; Gerber, D.E.; Bey, E.A.; Boothman, D.A. Leveraging an NQO1 bioactivatable drug for tumor-selective use of poly(ADP-ribose) polymerase inhibitors. Cancer Cell, 2016, 30(6), 940-952.
[237]
Muvarak, N.E.; Chowdhury, K.; Xia, L.; Robert, C.; Choi, E.Y.; Cai, Y.; Bellani, M.; Zou, Y.; Singh, Z.N.; Duong, V.H.; Rutherford, T.; Nagaria, P.; Bentzen, S.M.; Seidman, M.M.; Baer, M.R.; Lapidus, R.G.; Baylin, S.B.; Rassool, F.V. Enhancing the cytotoxic effects of PARP inhibitors with DNA demethylating agents - A potential therapy for cancer. Cancer Cell, 2016, 30(4), 637-650.
Related Journals
Current Pharmaceutical Design
Current Topics in Medicinal Chemistry
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Anti-Infective Agents
Coronaviruses
Recent Advances in Inflammation & Allergy Drug Discovery
Current Probiotics
Article Metrics
66
12
1
1